Department of Brain Sciences, Imperial College London, Du Cane Road 160, London, W12 0NN, UK.
Department of Biotechnology, University of Verona, Verona, Italy.
J Neuroinflammation. 2024 Apr 12;21(1):91. doi: 10.1186/s12974-024-03077-9.
Soluble CD27 is a promising cerebrospinal fluid inflammatory biomarker in multiple sclerosis. In this study, we investigate relevant immune and neuro-pathological features of soluble CD27 in multiple sclerosis.
Protein levels of soluble CD27 were correlated to inflammatory cell subpopulations and inflammatory cytokines and chemokines detected in cerebrospinal fluid of 137 patients with multiple sclerosis and 47 patients with inflammatory and non-inflammatory neurological disease from three independent cohorts. Production of soluble CD27 was investigated in cell cultures of activated T and B cells and CD27-knockout T cells. In a study including matched cerebrospinal fluid and post-mortem brain tissues of patients with multiple sclerosis and control cases, levels of soluble CD27 were correlated with perivascular and meningeal infiltrates and with neuropathological features.
We demonstrate that soluble CD27 favours the differentiation of interferon-γ-producing T cells and is released through a secretory mechanism activated by TCR engagement and regulated by neutral sphingomyelinase. We also show that the levels of soluble CD27 correlate with the representation of inflammatory T cell subsets in the CSF of patients with relapsing-remitting multiple sclerosis and with the magnitude of perivascular and meningeal CD27 + CD4 + and CD8 + T cell infiltrates in post-mortem central nervous system tissue, defining a subgroup of patients with extensive active inflammatory lesions.
Our results demonstrate that soluble CD27 is a biomarker of disease activity, potentially informative for personalized treatment and monitoring of treatment outcomes.
可溶性 CD27 是多发性硬化症中一种很有前途的脑脊液炎症生物标志物。本研究旨在探讨可溶性 CD27 在多发性硬化症中的相关免疫和神经病理学特征。
我们将可溶性 CD27 蛋白水平与在三个独立队列的 137 例多发性硬化症患者和 47 例炎症性和非炎症性神经系统疾病患者的脑脊液中检测到的炎症细胞亚群和炎症细胞因子及趋化因子进行了相关性分析。我们还研究了激活的 T 和 B 细胞及 CD27 敲除 T 细胞中的可溶性 CD27 产生情况。在一项纳入多发性硬化症患者和对照病例匹配的脑脊液和尸检脑组织的研究中，我们分析了可溶性 CD27 水平与血管周围和脑膜浸润以及神经病理学特征的相关性。
我们证明可溶性 CD27 有利于产生干扰素-γ的 T 细胞分化，通过 TCR 结合激活的分泌机制释放，并受中性鞘磷脂酶调控。我们还发现，可溶性 CD27 水平与复发缓解型多发性硬化症患者脑脊液中炎症性 T 细胞亚群的表现以及尸检中枢神经系统组织中血管周围和脑膜 CD27+CD4+和 CD8+T 细胞浸润的程度相关，这为广泛存在活跃炎症性病变的患者定义了一个亚组。
我们的研究结果表明，可溶性 CD27 是疾病活动的生物标志物，可能对个性化治疗和治疗效果监测具有重要意义。
